Prostate cancer remains the most common and second most fatal cancer among men in the United States. The long term goal of this study is to identify the mechanism of action for nutritional supplements that protect men from developing prostate cancer. Future prostate cancer prevention trials depend on identification of these pathways to facilitate drug development. Specific Aim 1: Gene expression patterns from prostate biopsies among men on nutritional supplements vs. placebo will be compared. Men will be randomized to take placebo, lycopene or fish oil supplements and prostate biopsies will be taken at initiation of the study and at three months. The primary outcome measure is a two-fold up or two-fold down change in gene expression, pre- and post-intervention; the proportion of men with this outcome will be compared between intervention and placebo groups. Using these criteria, we will identify candidate molecular targets for nutrition response pathways deserving further study. Specific Aim 2: Baseline gene expression patterns from initial prostate biopsies will be correlated with self-reported dietary intake. Based on previous epidemiologic, in vitro, and in vivo studies, we hypothesize that higher intakes of total energy, fat/meat/animal products, dairy/calcium, and lower intakes of fish, vegetables, tomatoes/lycopene, vitamin E, and selenium will be associated with particular gene expression profiles. Specific Aim 3: Nutritional supplementation, self-reported diet and gene expression patterns will be correlated with clinical progression of prostate cancer among men following a watchful waiting protocol. After the three-month intervention, we will follow each subject for up to an additional nine months (12 months total) for clinical progression of his prostate cancer (i.e. based on PSA kinetics, pathology, etc). Men will have standard clinical exams quarterly, and we will query each patient's physician regarding the status of the patient's prostate tumor at three-month intervals. Our laboratory has developed considerable expertise in genome-wide analysis of clinical needle biopsies from men with prostate cancer using a faithful RNA amplification method. The MENS study will use gene expression profiling in the context of a prospective randomized cohort study. Statistical methods will be used to combine epidemiologic dietary information with gene expression data, and to correlate nutritional interventions with gene expression data. Results will be confirmed with an independent assay of gene expression levels, quantitative polymerase chain reaction using the same clinical samples. Post trial follow-up of patients will determine the outcome of watchful waiting, and the correlation of gene expression in patients who do and do not exhibit clinical progression may lead to development of targeted therapeutics for prostate cancer. The DNA, serum, tissue samples and dietary data collected in this trial will be available for other planned future collaborative studies.